Entecavir downregulates interleukin-37 in patients with chronic active hepatitis B infection

J Int Med Res. 2020 Jan;48(1):300060519884157. doi: 10.1177/0300060519884157.

Abstract

Objectives: Interleukin-37 (IL-37) has been identified as a potent inhibitor of the immune response. This study aimed to examine IL-37 expression in patients with chronic active hepatitis B (CAHB), and explore its possible regulatory role during inflammation.

Methods: Peripheral blood mononuclear cells (PBMCs) were collected from control (n = 20) and CAHB patients (n = 30) before and after treatment with entecavir (EVT) for 24 weeks. The PBMCs were cultured with lipopolysaccharide and IL-37 expression was determined by real-time polymerase chain reaction and flow cytometry. The mRNA and protein concentrations of IL-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) in PBMCs were also measured.

Results: Levels of IL-37, IL-1β, IL-6, and TNF-α were significantly increased in the supernatant of PBMCs from patients with CAHB. IL-37 significantly reduced the expression of IL-1β, IL-6, and TNF-α. EVT resulted in regression of intraocular inflammation in patients with CAHB, associated with decreased production of IL-37.

Conclusion: These results suggest that increased expression of IL-37 was associated with the suppression of the inflammatory response in patients with CAHB. Furthermore, EVT treatment of CAHB was also correlated with downregulation of IL-37, indicating that EVT may partially alleviate the immune response by modulating IL-37 production.

Keywords: Chronic hepatitis B infection; IL-37; IL-6; TNF-α; entecavir; immune response.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Case-Control Studies
  • Cells, Cultured
  • Down-Regulation / drug effects
  • Down-Regulation / immunology
  • Female
  • Guanine / analogs & derivatives*
  • Guanine / pharmacology
  • Guanine / therapeutic use
  • Healthy Volunteers
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B Surface Antigens / immunology
  • Hepatitis B virus / immunology
  • Hepatitis B, Chronic / blood
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Hepatitis B, Chronic / virology
  • Humans
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism*
  • Leukocytes, Mononuclear / immunology*
  • Leukocytes, Mononuclear / metabolism
  • Lipopolysaccharides / immunology
  • Male
  • Middle Aged
  • Primary Cell Culture
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Treatment Outcome
  • Young Adult

Substances

  • Hepatitis B Surface Antigens
  • IL37 protein, human
  • Interleukin-1
  • Lipopolysaccharides
  • entecavir
  • Guanine